p53 chromatin epigenetic domain organization and p53 transcription.
Epigenetic organization represents an important regulation mechanism of gene expression. In this work, we show that the mouse p53 gene is organized into two epigenetic domains. The first domain is fully unmethylated, associated with histone modifications in active genes, and organized in a nucleosome-free conformation that is deficient in H2a/H2b, whereas the second domain is fully methylated, associated with deacetylated histones, and organized in a nucleosomal structure. In mitotic cells, RNA polymerase is depleted in domain II, which is folded into a higher-order structure and is associated with H1 histone, whereas domain I conformation is preserved. Similar results were obtained for cells treated with inhibitors of associated regulatory factors. These results suggest that depletion of RNA polymerase II is the result of a physical barrier due to the folding of chromatin in domain II. The novel chromatin structure in the first domain during mitosis also suggests a mechanism for marking active genes in successive cell cycles.
Su
Chia-Hsin
CH
Institute of Biochemistry and Molecular Biology, School of Life Science, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Shann
Yih-Jyh
YJ
Hsu
Ming-Ta
MT
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D019175:DNA Methylation; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D003851:Deoxyribonucleases / Q000378:metabolism; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism; D051379:Mice; D008938:Mitosis; D009690:Nucleic Acid Conformation; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012319:RNA Polymerase II / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D002843:Chromatin; D006657:Histones; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D012319:RNA Polymerase II; D003851:Deoxyribonucleases; D004264:DNA Topoisomerases, Type I